Papers by Benedetta Bodini
Journal of Nuclear Medicine, 2020
To develop a novel approach to generate individual maps of white matter (WM) innate immune cell a... more To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18 F-DPA-714 translocator protein (TSPO) positron emission tomography (PET), and to explore the relationship between these maps and individual trajectories of disability worsening in patients with multiple sclerosis (MS). Methods: Patients with MS (n=37), whose trajectories of disability worsening over the 2 years preceding study entry were calculated, and healthy controls (n=19) underwent magnetic resonance magnetic and 18 F-DPA-714 PET. A threshold of significant activation of 18 F-DPA-714 binding was calculated with a voxel-wise randomized permutation-based comparison between patients and controls, and used to classify each WM voxel in patients as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were employed to calculate the extent of activation in WM regions-of-interests and to classify each WM lesion as "DPA-active", "DPA-inactive" or "unclassified". Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM, (NAWM in patients=24.99.7%; WM in controls=14.07.8%, p<0.001). In patients with MS, the percentage of DPA+ voxels showed a significant increase from NAWM, to perilesional areas, T2 hyperintense lesions and T1 hypointense lesions (38.113.5%, 45.017.9%, and 51.922.9%, respectively, p<0.001). Among the 1379 T2 lesions identified, 512 were defined as DPAactive and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (OR=1.13, p=0.009), a higher percentage of DPA+ voxels in the NAWM (OR=1.16, p=0.009) and in T1-spin-echo lesions (OR=1.06, p=0.036), were significantly associated with a retrospective more severe clinical trajectory in patients with MS. Conclusion: A more severe trajectory of disability worsening in MS is associated with an innate immune cells activation inside and around WM lesions. 18 F-DPA-714 PET may provide a promising biomarker to identify patients at risk of severe clinical trajectory.
Multiple Sclerosis Journal
European Journal of Neurology
European Journal of Neurology
Coronavirus disease 2019 (COVID‐19), a multi‐organ disease caused by severe acute respiratory syn... more Coronavirus disease 2019 (COVID‐19), a multi‐organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID‐19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID‐19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long‐term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID‐19 Task Force intends to raise awareness of the potential impact of COVID‐19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.
Multiple Sclerosis Journal
Few cases of human papillomavirus (HPV) diseases have been reported in multiple sclerosis (MS) pa... more Few cases of human papillomavirus (HPV) diseases have been reported in multiple sclerosis (MS) patients treated with fingolimod. We describe a case series of 16 MS patients (11 women, 5 men) developing HPV lesions after the onset of fingolimod, without previous HPV history. Fingolimod had to be discontinued in six patients. Six patients received vaccination for HPV, with good tolerance. Our report highlights that systematic HPV screening and discussion about HPV vaccination before fingolimod onset are crucial. In case of occurrence of HPV lesions during fingolimod treatment, a comprehensive workup of HPV disease is necessary, with discussion of HPV vaccination to prevent secondary lesions. Prevalence studies of HPV lesions are needed in MS patients with the different disease-modifying therapies.
Nature Reviews Neurology
Following the impressive progress in the treatment of relapsing–remitting multiple sclerosis (MS)... more Following the impressive progress in the treatment of relapsing–remitting multiple sclerosis (MS), the major challenge ahead is the development of treatments to prevent or delay the irreversible accumulation of clinical disability in progressive forms of the disease. The substrate of clinical progression is neuro-axonal degeneration, and a deep understanding of the mechanisms that underlie this process is a precondition for the development of therapies for progressive MS. PET imaging involves the use of radiolabelled compounds that bind to specific cellular and metabolic targets, thereby enabling direct in vivo measurement of several pathological processes. This approach can provide key insights into the clinical relevance of these processes and their chronological sequence during the disease course. In this Review, we focus on the contribution that PET is making to our understanding of extraneuronal and intraneuronal mechanisms that are involved in the pathogenesis of irreversible neuro-axonal damage in MS. We consider the major challenges with the use of PET in MS and the steps necessary to realize clinical benefits of the technique. In addition, we discuss the potential of emerging PET tracers and future applications of existing compounds to facilitate the identification of effective neuroprotective treatments for patients with MS. In this Review, Bodini et al. discuss the contribution that PET is making to our understanding of mechanisms involved in the pathogenesis of irreversible neuro-axonal damage that underlies progression in multiple sclerosis. PET enables direct in vivo measurement of key processes in the pathogenesis of neurodegeneration in multiple sclerosis (MS). PET imaging of neuroinflammatory processes has shown that innate immune cell activation inside and outside visible lesions is a relevant pathogenic mechanism in MS, even in the earliest stages of the disease. Novel PET tracers that specifically target innate immune cells, lymphocytes, metabolic pathways, endothelial molecules and active astrocytes could provide new insights into the role of inflammation in neurodegeneration in MS. PET imaging of myelin in patients with MS has shown that myelin loss and failure of myelin repair can contribute to the accumulation of clinical disability. PET imaging of the mitochondria and synaptic vesicles can be used to detect the earliest metabolic and structural changes in neurons in MS. PET imaging of pathological processes could provide robust outcome measures in clinical trials of drugs designed to delay or prevent neurodegeneration in MS. PET enables direct in vivo measurement of key processes in the pathogenesis of neurodegeneration in multiple sclerosis (MS). PET imaging of neuroinflammatory processes has shown that innate immune cell activation inside and outside visible lesions is a relevant pathogenic mechanism in MS, even in the earliest stages of the disease. Novel PET tracers that specifically target innate immune cells, lymphocytes, metabolic pathways, endothelial molecules and active astrocytes could provide new insights into the role of inflammation in neurodegeneration in MS. PET imaging of myelin in patients with MS has shown that myelin loss and failure of myelin repair can contribute to the accumulation of clinical disability. PET imaging of the mitochondria and synaptic vesicles can be used to detect the earliest metabolic and structural changes in neurons in MS. PET imaging of pathological processes could provide robust outcome measures in clinical trials of drugs designed to delay or prevent neurodegeneration in MS.
European Journal of Neurology
Immunization by means of vaccination is a global health success story, saving millions of lives e... more Immunization by means of vaccination is a global health success story, saving millions of lives every year. In this regard, the epidemiology of measles, rabies, polio, rubella, varicella, influenza and mumps infections, all of which can harm the nervous system, could be contained by global vaccination campaigns. In addition, toxoid vaccines against bacterial toxins such as tetanus and diphtheria are indispensable and effective interventions for toxin-mediated neurologic diseases.
Choroid plexuses (CP) are structures of the ventricles of the brain which produce most of the cer... more Choroid plexuses (CP) are structures of the ventricles of the brain which produce most of the cerebrospinal fluid (CSF). Several postmortem and in vivo studies have pointed towards their role in the inflammatory process in multiple sclerosis (MS). Automatic segmentation of CP from MRI thus has high value for studying their characteristics in large cohorts of patients. To the best of our knowledge, the only freely available tool for CP segmentation is FreeSurfer but its accuracy for this specific structure is poor. In this paper, we propose to automatically segment CP from non-contrast enhanced T1-weighted MRI. To that end, we introduce a new model called "Axial-MLP" based on an assembly of Axial multi-layer perceptrons (MLPs). This is inspired by recent works which showed that the self-attention layers of Transformers can be replaced with MLPs. This approach is systematically compared with a standard 3D U-Net, nnU-Net, Freesurfer and FastSurfer. For our experiments, we mak...
European Journal of Neurology
Multiple Sclerosis Journal
Background: Diffusion-weighted 1H magnetic resonance spectroscopy (DW-MRS) allows to quantify cre... more Background: Diffusion-weighted 1H magnetic resonance spectroscopy (DW-MRS) allows to quantify creatine-phosphocreatine brain diffusivity (ADC(tCr)), whose reduction in multiple sclerosis (MS) has been proposed as a proxy of energy dysfunction. Objective: To investigate whether thalamic ADC(tCr) changes are associated with thalamo-cortical tract damage in MS. Methods: Twenty patients with MS and 13 healthy controls (HC) were enrolled in a DW-MRS and DW imaging (DWI) study. From DW-MRS, ADC(tCr) and total N-acetyl-aspartate diffusivity (ADC(tNAA)) were extracted in the thalami. Three thalamo-cortical tracts and one non-thalamic control tract were reconstructed from DWI. Fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD), reflecting microstructural integrity, were extracted for each tract. Associations between thalamic ADC(tCr) and tract metrics were assessed using linear regression models adjusting for age, sex, thalamic volume, thalamic ADC(tNAA), and trac...
Lecture Notes in Computer Science, 2018
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). A reliabl... more Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). A reliable measure of the tissue myelin content is therefore essential to understand the physiopathology of MS, track progression and assess treatment efficacy. Positron emission tomography (PET) with [ 11 C]PIB has been proposed as a promising biomarker for measuring myelin content changes in-vivo in MS. However, PET imaging is expensive and invasive due to the injection of a radioactive tracer. On the contrary, magnetic resonance imaging (MRI) is a non-invasive, widely available technique, but existing MRI sequences do not provide, to date, a reliable, specific, or direct marker of either demyelination or remyelination. In this work, we therefore propose Sketcher-Refiner Generative Adversarial Networks (GANs) with specifically designed adversarial loss functions to predict the PET-derived myelin content map from a combination of MRI modalities. The prediction problem is solved by a sketch-refinement process in which the sketcher generates the preliminary anatomical and physiological information and the refiner refines and generates images reflecting the tissue myelin content in the human brain. We evaluated the ability of our method to predict myelin content at both global and voxel-wise levels. The evaluation results show that the demyelination in lesion regions and myelin content in normalappearing white matter (NAWM) can be well predicted by our method. The method has the potential to become a useful tool for clinical management of patients with MS.
J Neurol Neurosurg Psychiat, 2010
Nearly 100 cases of atopic myelitis have been reported in Japan. However, it has only been descri... more Nearly 100 cases of atopic myelitis have been reported in Japan. However, it has only been described in two non-Japanese patients, both from Western Europe. We report a European individual who developed cervical myelitis while resident in Japan. This showed a partial response to corticosteroids. There was no clinical or radiological dissemination for over 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;emsp14;years, at which time she had a brainstem relapse caused by a new lesion in the medulla oblongata. The patient had high serum total IgE with evidence of allergy to several antigens, including house dust mite and soya. It is possible that the incidence of atopic myelitis may be underestimated where it is not standard practice to measure serum IgE levels in patients with myelopathy. Such cases will instead be subsumed into the diagnostic category of clinically isolated syndrome. However, it remains uncertain whether atopic myelitis is a distinct disease or falls within the spectrum of demyelinating diseases. Further studies are required to fully elucidate the relationship between atopy and the incidence and severity of CNS inflammatory disorders.
Annals of Neurology, 2016
Annals of Neurology, 2016
Quantitative in vivo imaging of myelin loss and repair in patients with multiple sclerosis (MS) i... more Quantitative in vivo imaging of myelin loss and repair in patients with multiple sclerosis (MS) is essential to understand the pathogenesis of the disease and to evaluate promyelinating therapies. Selectively binding myelin in the central nervous system white matter, [(11) C]PIB can be used as a positron emission tomography (PET) tracer to explore myelin dynamics in MS. Patients with active relapsing-remitting MS (n=20) and healthy controls (n=8) were included in a longitudinal trial combining PET with [(11) C]PIB and magnetic resonance imaging. Voxel-wise maps of [(11) C]PIB distribution volume ratio, reflecting myelin content, were derived. Three dynamic indices were calculated for each patient: the global index of myelin content change; the index of demyelination; and the index of remyelination. At baseline, there was a progressive reduction in [(11) C]PIB binding from the normal-appearing white matter to MS lesions, reflecting a decline in myelin content. White matter lesions were characterized by a centripetal decrease in the tracer binding at the voxel level. During follow-up, high between-patient variability was found for all indices of myelin content change. Dynamic remyelination was inversely correlated with clinical disability (p=0.006 and beta-coefficient=-0.67 with the Expanded Disability Status Scale; p=0.003 and beta-coefficient=-0.68 with the MS Severity Scale), whereas no significant clinical correlation was found for the demyelination index. [(11) C]PIB PET allows quantification of myelin dynamics in MS and enables stratification of patients depending on their individual remyelination potential, which significantly correlates with clinical disability. This technique should be considered to assess novel promyelinating drugs. This article is protected by copyright. All rights reserved.
Neurology, Jan 16, 2015
The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early ... more The temporal relationship between white matter (WM) and gray matter (GM) damage in vivo in early primary progressive multiple sclerosis (PPMS) was investigated testing 2 hypotheses: (1) WM tract abnormalities predict subsequent changes in the connected cortex ("primary WM damage model"); and (2) cortical abnormalities predict later changes in connected WM tracts ("primary GM damage model"). Forty-seven patients with early PPMS and 18 healthy controls had conventional and magnetization transfer imaging at baseline; a subgroup of 35 patients repeated the protocol after 2 years. Masks of the corticospinal tracts, genu of the corpus callosum and optic radiations, and of connected cortical regions, were used for extracting the mean magnetization transfer ratio (MTR). Multiple regressions within each of 5 tract-cortex pairs were performed, adjusting for the dependent…
Uploads
Papers by Benedetta Bodini